The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Cell-type-specific metabolic labeling of nascent proteomes in vivo
Abstract
Although advances in protein labeling methods have made it possible to measure the proteome of mixed cell populations, it has not been possible to isolate cell-type-specific proteomes in vivo. This is because the existing methods for metabolic protein labeling in vivo access all cell types. We report the development of a transgenic mouse line where Cre-recombinase-induced expression of a mutant methionyl-tRNA synthetase (L274G) enables the cell-type-specific labeling of nascent proteins with a non-canonical amino-acid and click chemistry. Using immunoblotting, imaging and mass spectrometry, we use our transgenic mouse to label and analyze proteins in excitatory principal neurons and Purkinje neurons in vitro (brain slices) and in vivo. We discover more than 200 proteins that are differentially regulated in hippocampal excitatory neurons by exposing mice to an environment with enriched sensory cues. Our approach can be used to isolate, analyze and quantitate cell-type-specific proteomes and their dynamics in healthy and diseased tissues.
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“Several key proteins (e.g., APP, Grm5) linked to neurodevelopmental or neurodegenerative disorders were also identified [158].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
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“Proteins within a specific cell type can be uniquely labeled in vivo via BONCAT (Fig. 2) and isolated from a complex tissue, such as the brain, for MS-based proteomics.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
In the citing paper
“The Camk2a hippocampal proteome was significantly enriched with proteins represented by neuronal components, such as synaptic transmission and synaptic plasticity.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
In the citing paper
“Recently, BONCAT was utilized to characterize excitatory and inhibitory neuronal proteomes in adult mice [158, 159].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
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Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124
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Metadata
- Authors
- Alvarez-Castelao, B., Schanzenbächer, C. T., Hanus, C., Glock, C., tom Dieck, S., Dörrbaum, A. R., Bartnik, I., Nassim-Assir, B., Ciirdaeva, E., Mueller, A., Dieterich, D. C., Tirrell, D. A., Langer, J. D., & Schuman, E. M.
- Affiliations
- Max Planck Institute of Biophysics (DE)
- Max Planck Institute for Brain Research (DE)
- Center for Behavioral Brain Sciences (DE)
- California Institute of Technology (US)
- Corresponding author
- Schuman, Erin M
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2017-11-06
- Volume
- 35
- Issue
- 12
- Pages
- 1196-1201
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2765371514
- Semantic Scholar
- 2688eacdb4dbfc63c3da8b32bdde84e7bfbfaea1
- Cited by
- 219
- References
- 50
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 40 · 2023: 27 · 2022: 25 · 2021: 19 · 2020: 26 · 2019: 17 · 2018: 17 · 2017: 2
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-CE16-0009)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Keywords
- click chemistry, transgenic mice, Cre recombinase, Purkinje cells, hippocampus
- MeSH terms
- Amino Acids, Animals, Female, Gene Expression Regulation, Male, Methionine-tRNA Ligase, Mice, Transgenic, Neurons, Integrases, Proteome, Proteomics, Mice, Click Chemistry
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